The author of an editorial of a case series describing severe bradycardia and loss of consciousness following ondansetron administration states the original paper does not describe the rate at which ondansetron was given. It is not uncommon for residents to administer ondansetron as a bolus perioperatively, but the author wants clinicians to be aware that ondansetron 4 to 8 mg IV should be administered over 2 to 5 min and not as a bolus or in less than 30 seconds. Instead, the editorial recommends ondansetron over 2 to 5 minutes to decrease the incidence of potentially life-threatening adverse effects. [1]
A case study from 2001 described the experience of a 55-year-old woman with metastatic breast cancer who was administered 8 mg dexamethasone and 8 mg ondansetron IV push as an antiemetic during chemotherapy. The patient had no history of seizures or heart disease. On the day following administration of ondansetron and dexamethasone, the patient developed tonic-clonic seizures, which lasted for a duration of two minutes. The suspected underlying reason was considered to be brain metastasis or metabolic abnormality, but a definite cause was not established and the patient was discharged. The patient developed seizures once again; a detailed exam found no apparent abnormalities. Due to persistent vomiting, ondansetron was changed to metoclopramide, resulting in a resolution of vomiting. The patient's health care providers suspected seizures may have been an adverse event of a drug, possibly ondansetron. Following the discontinuation of ondansetron, no further seizures were reported. Thus, the authors believed ondansetron was the likely cause. [2]
Another case report was cited within a randomized trial. A 65-year-old woman with nasopharyngeal carcinoma received an IV push of 8 mg (0.15 mg/kg) of undiluted ondansetron and 20 mg IV dexamethasone on day one of chemotherapy. Ondansetron IV push was administered prior to the initial cisplatin dose. Following this, the patient received ondansetron 8 mg orally at 8-hour intervals for four days. This same routine appears to have been followed for the second cycle. However, for the third cycle, on the third day, the seventh dose of ondansetron was slowly injected intravenously. The patient subsequently developed dystonia of the jaw, stiffness of the limbs, inability to speak, anxiety, and a burning sensation in the face and hands. The episode lasted 1-2 minutes and resolved spontaneously. The subsequent doses of ondansetron, for the rest of the third cycle and for the fourth cycle were administered diluted over a 15-min intravenous infusion, with no additional adverse events. The authors suspected a correlation between direct IV ondansetron administration and the occurrence of the aforementioned adverse events, suggesting a possible relation between the effects and high plasma levels of the drug. [3], [4]
A prospective cohort study (N= 261) assessed the effects of ondansetron on cardiac safety in children and pregnant women. Patients were divided into three cohorts: pediatric oncology (n= 98), pregnant women (n= 62), and pediatric surgery (n= 101). Of these three, only pregnant women were permitted to receive 4-8 mg ondansetron. The route of administration is not clearly defined. It appears IV push was permitted, but patient characteristics list that nearly 100% of patients received an IV bolus, substantially limiting the conclusions that may be derived from this study regarding the safety of a high dose ondansetron IV push. The authors concluded that, although rare, ondansetron may be associated with transient QT prolongation. No associations between clinical variables and the incidence of QT prolongation were observed within individual cohorts. [4]